Proinsulin is the immediate precursor in the biosynthesis of insulin. The propeptide is processed to the biologically active molecule by a mechanism of limited proteolytic cleavage. The enzymes participating in the conversion process are not known. Recently we have identified a serine protease - plasminogen activator (P.A.) - in rat islets of Langerhans. Secretion of the islet enzyme is modulated bY glucose and certain other regulators of insulin release, and beta-cells are the probable source of the enzyme. Preliminary findings indicate a possible function for P.A. in the processing of proinsulin. Insulin biosynthesis and P.A. production from isolated rat islets of Langerhans in response to modulators of insulin release and some other agents will be examined to elucidate the relationship of the enzyme to insulin biosynthesis. The islet cell which produces the glucose-responsive enzyme will be identified utilizing histochemical and fibrinolytic methods. The islet P.A. will be characterized and the enzymatic features analyzed in comparison with urokinase. The role of islet P.A. in processing of proinsulin would be investigated in vitro to define the requirements for plasminogen and the conditions for optimal conversion. Preliminary electrophoretic characterization of the products formed during the conversion process would be carried out. Plasminogen, the only known substrate for activator, has not been identified in the islets but appears to be necessary for in vitro conversion. The processing of proinsulin by islets would be examined to determine if intact islets do require plasminogen for the conversion and the possible source for this plasminogen. The role of P.A. in insulin biosynthesis would be evaluated from these studies.